Suicidal behavior places a staggering burden on individuals, families, and society. Although previous research has identified numerous risk factors for suicidal behavior, research that can draw strong causal inferences about such risk factors is needed for the most effective prevention of suicidal behavior. Several genetically-informed, Swedish population registries will be merged to form an unprecedented dataset of every individual born in Sweden from 1973 to 1996 (NH2,100,000) that is large enough to investigate the relatively rare, yet costly suicidal behavior. Early risk factors to be examined include maternal stress exposure pregestation, prenatally, and during the first 4 years of postnatal life. Stress is defined as the death or hospitalization of a first degree relative or partner of the mother. Suicidal behavior outcomes include definite and uncertain suicide attempts, suicide completions and accidental deaths. First, Cox Proportional Survival Analyses will be employed to examine the association between timing of stress exposure and suicidal behavior. Measures of early offspring, family, and community- level risks (e.g. parental age and socioeconomic status) will be included as covariates. Identifying periods of early development that are at heightened vulnerability would provide useful information for the support or rejection of different etiological hypotheses of suicide. Second, alternative hypotheses of the statistical associations will be tested. We will examine how early stress exposure covaries with other known risk factors for suicidal behavior, including maternal and paternal suicidal behavior. Further, because the dataset includes information on the biological relatedness of each individual with all of their family, the current project will also utilize powerful family-based, quasi-experimental methods to account for alternative causal hypotheses. In particular, the sibling comparison design, by examining differentially exposed siblings, will provide increased control of unmeasured background factors (both environmental and genetic) that may influence the association between early maternal stress and offspring suicidality. Third, the potential mediating effects of adverse birth outcomes, such as preterm birth and low birth weight, will be examined to further clarify the relations between early stress exposure and later suicidal behavior. The training plan will support instruction in advanced quasi- experimental and epidemiological methods, education in translational research and theory including animal studies of early stress, and hands-on clinical work with relevant populations. Findings from the current project will provide information to improve prevention programs and increase our understanding of the etiology of suicidal behavior. PUBLIC HEALTH RELEVANCE: Suicide reduction is a public health priority, but the effective prevention of suicidal behavior requires the identification of risk factors that are causally linked to suicidal behaviors. Previous research has been unable to draw strong causal inferences regarding risk factors because of empirical restrictions and limited data. In order to improve prevention programs and our understanding of the etiology of suicidal behavior, the current proposal uses novel analytical and methodological approaches to understand early risk factors for suicidal behavior in a study of every individual in Sweden from 1973 to 1996 (NH2,100,000).